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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
SOHO State of the Art Updates and Next Questions: New Targetable Pathways in Chronic Lymphocytic Leukemia
1Division of Hematology, Department of Medicine, Stanford University, Palo Alto, CA.
Abstract:
Regulatory approvals of Bruton tyrosine kinase (BTK) inhibitors and BCL2 inhibitors have transformed the therapeutic paradigm in chronic lymphocytic leukemia (CLL). However, despite significant improvement, treatment discontinuations due to an acquired resistance mutation or intolerance to these agents are common. Those who are refractory and/or intolerant to both these classes of drugs - the "double exposed/refractory" patients - pose a real challenge in clinical practice and are in dire need of novel therapeutic approaches. In this manuscript, we review the ongoing efforts addressing this unmet clinical need including the ongoing development of non-covalent BTK inhibitors, BTK degraders, novel BH3-mimetics, therapeutic antibodies targeting novel antigens and immune cell enabling therapies.
Insights
New therapies are needed for chronic lymphocytic leukemia (CLL) patients resistant to Bruton tyrosine kinase (BTK) and BCL2 inhibitors. Research is exploring novel BTK inhibitors, degraders, and immune therapies to overcome treatment challenges.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Bruton tyrosine kinase (BTK) and BCL2 inhibitors have revolutionized chronic lymphocytic leukemia (CLL) treatment.
- Treatment discontinuation due to resistance or intolerance is a significant clinical challenge.
- A subset of patients, termed "double exposed/refractory," require novel therapeutic strategies.
Purpose of the Study:
- To review current and emerging therapeutic strategies for CLL patients refractory or intolerant to BTK and BCL2 inhibitors.
- To highlight unmet clinical needs in managing difficult-to-treat CLL cases.
- To provide an overview of novel drug development pipelines.
Main Methods:
- Literature review of ongoing research and clinical trials.
- Analysis of emerging therapeutic classes targeting CLL.
- Synthesis of information on novel agents and treatment approaches.
Main Results:
- Several novel therapeutic approaches are under investigation for double exposed/refractory CLL.
- These include non-covalent BTK inhibitors, BTK degraders, and novel BH3-mimetics.
- Therapeutic antibodies and immune cell-based therapies are also being explored.
Conclusions:
- Addressing the needs of double exposed/refractory CLL patients is critical.
- Ongoing development of diverse novel therapies offers promise for improved outcomes.
- Further research and clinical trials are essential to validate these new treatment modalities.
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